PUBLICATION

The spinster homolog, two of hearts, is required for sphingosine 1-phosphate signaling in zebrafish

Authors
Osborne, N., Brand-Arzamendi, K., Ober, E.A., Jin, S.W., Verkade, H., Holtzman, N.G., Yelon, D., and Stainier, D.Y.
ID
ZDB-PUB-081217-22
Date
2008
Source
Current biology : CB   18(23): 1882-1888 (Journal)
Registered Authors
Holtzman, Nathalia Glickman, Jin, Suk-Won, Ober, Elke, Osborne, Nick, Stainier, Didier, Verkade, Heather, Yelon, Deborah
Keywords
DEVBIO; SIGNALING
MeSH Terms
  • Animals
  • Gene Expression Regulation, Developmental*
  • Heart/embryology*
  • Lysophospholipids/metabolism*
  • Membrane Proteins/chemistry
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Mutation
  • Organogenesis
  • Phenotype
  • Receptors, Lysosphingolipid/genetics
  • Receptors, Lysosphingolipid/metabolism
  • Signal Transduction*
  • Sphingosine/analogs & derivatives*
  • Sphingosine/metabolism
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
19062281 Full text @ Curr. Biol.
Abstract
The bioactive lipid sphingosine 1-phosphate (S1P) and its G protein-coupled receptors play critical roles in cardiovascular, immunological, and neural development and function [1-6]. Despite its importance, many questions remain about S1P signaling, including how S1P, which is synthesized intracellularly, is released from cells. Mutations in the zebrafish gene encoding the S1P receptor Miles Apart (Mil)/S1P(2) disrupt the formation of the primitive heart tube [5]. We find that mutations of another zebrafish locus, two of hearts (toh), cause phenotypes that are morphologically indistinguishable from those seen in mil/s1p2 mutants. Positional cloning of toh reveals that it encodes a member of the Spinster-like family of putative transmembrane transporters. The biological functions of these proteins are poorly understood, although phenotypes of the Drosophila spinster and zebrafish not really started mutants suggest that these proteins may play a role in lipid trafficking [7, 8]. Through gain- and loss-of-function analyses, we show that toh is required for signaling by S1P(2). Further evidence indicates that Toh is involved in the trafficking or cellular release of S1P.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes